ExPert ConsEnsus on the management of Advanced clear-cell RenaL celL carcinoma: INDIAn Perspective (PEARL-INDIA).

In advanced Renal Cell Carcinoma (aRCC), systemic therapy is the mainstay of treatment, with no or little role for surgery in these patients. Tyrosine kinase inhibitors (TKIs) and immune-oncological (IOs) therapies, either alone or in combination, are recommended in these patients depending on patient and tumour factors. The sequencing of therapies is critical in RCC because the choice of subsequent line therapy is heavily dependent on the response and duration of the previous treatment. There are additional barriers to RCC treatment in India. Immunotherapy is the cornerstone of treatment in ccRCC, but it is prohibitively expensive and not always reimbursed, effectively putting it out of reach for the vast majority of eligible patients in India. Furthermore, in advanced RCC (particularly the clear cell variety), Indian oncologists consider the disease burden of the patients, which is particularly dependent on the quantum of the disease load, clinical symptoms, and performance status of the patient, before deciding on treatment. There are no India-specific guidelines for clear cell RCC (ccRCC) treatment or the positioning and sequencing of molecules in the management of advanced ccRCC that take these country-specific issues into account. The current consensus article provides expert recommendations and treatment algorithms based on existing clinical evidence, which will be useful to specialists managing advanced ccRCC.

The effectiveness of NEPA in the prevention of chemotherapy-induced nausea vomiting among chemo naive patients in an Indian setting.

BACKGROUND: Chemotherapy induced nausea- vomiting (CINV) is considered as the most common, feared and most troublesome side effect of chemotherapy. NEPA (NEtupitant 300 mg + PAlonosetron 0.50 mg) is the first commercially available oral fixed-dose combination (FDC) of two active antiemetic agents in India. The present study was planned to evaluate the effectiveness of NEPA in the real world setting of India. METHODS: This was a multicentric retrospective study conducted in two centers in India. The data of all chemonaive patients, who were prescribed NEPA was analyzed. Effectiveness i.e. complete response and complete protection in controlling overall, acute and delayed phase was analyzed. RESULTS: A total of 329 patients were enrolled in the study. 260 received highly emetogenic chemotherapy (HEC) regimen and 69 received moderately emetogenic chemotherapy (MEC) regimen. Among all the enrolled patients, complete response in acute, delayed and overall phase was 93, 85.71 and 85.41% respectively; and completed protection was 88.44, 81.76 and 80.54% respectively. Those who received HEC regimen, the completed response and complete protection in overall phase was 84.61 and 79.61% respectively and those who received MEC regimen the completed response and complete control in overall phase was 84.05 and 84.05% respectively. CONCLUSION: A single oral dose of NEPA targeting dual pathways showed effective control of nausea-vomiting in patients on the HEC and MEC regimens and had good control over nausea-vomiting in acute, delayed and overall phase of nausea-vomiting.

Efficacy and Safety of Nanosomal Docetaxel Lipid Suspension (NDLS) versus Conventional Docetaxel as Neoadjuvant and Adjuvant Therapy for Primary Operable Breast Cancer.

Objective: Nanosomal docetaxel lipid suspension (NDLS) is a novel formulation developed to overcome toxicity issues caused by excipients (polysorbate 80 and ethanol) present in commercially available docetaxel formulation. We conducted a prospective, observational study to compare the outcomes of nanosomal docetaxel lipid suspension (NDLS)-based versus conventional docetaxel-based chemotherapy in primary operable breast cancer. Methods: Sixty adult women with newly diagnosed stage IIb-III breast cancer were included. Patients received NDLS-based (n=30) or docetaxel-based (n=30) chemotherapy. Patients received (1) four cycles of preoperative doxorubicin and cyclophosphamide (AC) followed by four cycles of NDLS or docetaxel (T) and surgery (neoadjuvant AC→NDLS [n=9], or neoadjuvant AC→T [n=10]), or (2) four cycles of preoperative AC followed by surgery and postoperative NDLS or T (neoadjuvant AC→adjuvant NDLS [n=14], or neoadjuvant AC→adjuvant T [n=15]), or (3) surgery followed by postoperative AC→NDLS or T (adjuvant AC→NDLS [n=7], or adjuvant AC→T [n=5]) regimens. The study outcomes were pathological complete response (pCR) rates, clinical overall response rates (ORR), disease-free survival (DFS), overall survival (OS), and adverse event (AE) profile. Results: For neoadjuvant AC→T (n=10) vs neoadjuvant AC→NDLS (n=9), the pCR rates were 100% each, and the ORR were 100% vs 88.9% (p=1.0). All patients were alive at 6 months, and the median OS was not reached. Three patients had progressive disease (T: n=2, NDLS: n=1) with a DFS of 12 weeks in all three patients. Grade 3 infusion-related reactions were seen in five patients (16.7%) in T vs none in NDLS arms. Conclusion: NDLS-based neo/adjuvant chemotherapy was efficacious in the treatment of primary operable breast cancer and showed comparable pCR, ORR, DFS and OS rates versus conventional docetaxel. NDLS was better tolerated than conventional docetaxel.

Second-line treatment of advanced hepatocellular carcinoma: Time for more individualized treatment options?

Hepatocellular carcinoma (HCC) is the most frequently diagnosed primary tumor of the liver and is usually detected as advanced disease. It is an aggressive disease that often progresses rapidly when it fails to respond to treatment. As such, patients have limited opportunities to try different subsequent-line treatment regimens. In the last 5 years, the number of agents and/or regimens available for the treatment of advanced HCC has significantly increased, which has made treatment choices for this patient population increasingly complex. In the second-line setting, several phase III trials of regorafenib (RESORCE), ramucirumab (REACH/REACH-2), and cabozantinib (CELESTIAL) have demonstrated clinically meaningful survival benefits in patients with the disease. However, the median overall survival of patients with advanced HCC remains unchanged at approximately 12 mo from the start of systemic second-line therapy, with a limited duration of response. Evidence from the REACH/REACH-2 trials demonstrated for the first time that baseline alpha-fetoprotein (AFP) levels can be used as an identification factor to select those who are likely to benefit the most from ramucirumab treatment. Ramucirumab is both well tolerated and efficacious and has a clinically acceptable safety profile. Therefore, it should be considered an option for patients with AFP levels ≥ 400 ng/mL.

CONCORDANCE: A real-world evidence study to evaluate the concordance of detecting epidermal growth factor receptor (EGFR) mutation by circulating tumor DNA* versus tissue biopsy in patients with metastatic non-small cell lung cancer.

Background: Molecular tissue testing in non-small cell lung cancer (NSCLC) is done for the assessment of epidermal growth factor receptor (EGFR) mutation. EGFR mutation status is the basis for deciding the targeted treatment option for patients with metastatic NSCLC. The nonavailability of tissue samples and contraindications for biopsy pose a significant challenge. Hence, circulating tumor DNA (ctDNA) by liquid biopsy can be a viable alternative for NSCLC patients. Methods: This study was conducted at 15 sites across India. EGFR mutation testing from plasma was done as part of the study at the central laboratory by the next-generation sequencing (NGS) method, and EGFR mutation test results from tissue samples (done as part of routine practice) were recorded for all the patients. Results: Out of the total patients enrolled (N = 245), the majority (64.5%, n = 158) were men. The median age of patients was 58.0 (range: 26-84) years. The concordance between plasma and tissue testing was found to be 82.9% (95% confidence interval [CI]: 77.55, 87.45). The sensitivity and specificity of NGS were 68.4% (95% CI: 56.92, 78.37) and 90.1% [95% CI: 84.36, 94.21), respectively. Plasma testing detected 1.2% (n = 3) and tissue sample testing detected 2.4% (n = 6) positive status of exon 20 T790M EGFR mutation. Out of the total number of patients enrolled, 25 were tissue positive and plasma negative, while 16 were plasma positive and tissue negative. Conclusions: "> This real-world study in Indian patients suggests that plasma testing for EGFR mutation analysis is a viable diagnostic option in newly diagnosed advanced/metastatic NSCLC patients. The noninvasive plasma procedure in patients without available/evaluable tumor sample may enable more patients to receive appropriate targeted therapies by providing clinicians with valuable insights into the patient's tumor mutation status. ClinicalTrials.gov Identifier: NCT03562819.

Practical Consensus Recommendations for Optimizing Risk versus Benefit of Chemotherapy in Patients with HR Positive Her2 Negative Early Breast Cancer in India.

Breast cancer is a public health challenge globally as well as in India. Improving outcome and cure requires appropriate biomarker testing to assign risk and plan treatment. Because it is documented that significant ethnic and geographical variations in biological and genetic features exist worldwide, such biomarkers need to be validated and approved by authorities in the region where these are intended to be used. The use of western guidelines, appropriate for the Caucasian population, can lead to inappropriate overtreatment or undertreatment in Asia and India. A virtual meeting of domain experts discussed the published literature, real-world practical experience, and results of opinion poll involving 185 oncologists treating breast cancer across 58 cities of India. They arrived at a practical consensus recommendation statement to guide community oncologists in the management of hormone positive (HR-positive) Her2-negative early breast cancer (EBC). India has a majority (about 50%) of breast cancer patients who are diagnosed in the premenopausal stage (less than 50 years of age). The only currently available predictive test for HR-positive Her2-negative EBC that has been validated in Indian patients is CanAssist Breast. If this test gives a score indicative of low risk (< 15.5), adjuvant chemotherapy will not increase the chance of metastasis-free survival and should not be given. This is applicable even during the ongoing COVID-19 pandemic.

Individualized Chemotherapy Benefit Prediction by EndoPredict in Patients With Early Breast Cancer in an Indian Cohort.

PURPOSE: There are new advancements in the modulation of the treatment of patients with early-stage breast cancer, including the use of several molecular profiling tests to identify or select those patients who require additional adjuvant chemotherapy together with hormonal therapy on the basis of a recurrence score. One such tool is EndoPredict (Myriad Genetics; Salt Lake City, UT), which provides support in clinical decision making. The objective of this analysis was to study the landscape of absolute chemotherapy benefit and the likelihood of recurrence within 5 to 15 years in Indian patients with breast cancer who are undergoing EndoPredict testing. PATIENTS AND METHODS: This study included 308 patients with hormone-positive, human epidermal growth factor receptor 2-negative early breast cancer. Their postsurgical blocks were analyzed using the EndoPredict test. The MEDCALC statistical tool (Panum Education; Seoul, Republic of Korea) was used to estimate the correlation coefficient and to conduct multiple regression analysis. RESULTS: On the basis of the EndoPredict EPclin Risk Score, 52.12% of patients were classified as being in the low-risk category and could safely forgo adjuvant chemotherapy. For every unit increase in the EPclin Risk Score, the percentage increase in absolute chemotherapy benefit was 6.82%. Similarly, the correlation between the likelihood of recurrence within 5 to 15 years and the EPclin Risk Score suggested that there is a 10.34% increase in recurrence for each unit of EPclin Risk Score. CONCLUSION: The EPclin Risk Score has good prognostic and predictive power; it also provides the range of chemotherapy benefit for Indian patients.

Efficacy and Safety of Nanosomal Docetaxel Lipid Suspension-Based Chemotherapy in Sarcoma: A Multicenter, Retrospective Study.

OBJECTIVE: To evaluate the efficacy and safety of nanosomal docetaxel lipid suspension (NDLS, DoceAqualip) based chemotherapy in patients with sarcoma. METHODS: In this retrospective, multicenter (6 centers), observational study, we analyzed the medical charts of adult patients of either sex, who were treated with NDLS (75 mg/m2 in 3-weekly cycles) based chemotherapy for the treatment of sarcoma. The efficacy outcomes were overall response rate (ORR: complete response (CR) + partial response (PR)) and disease control rate (DCR: CR + PR + stable disease (SD)) in patients who received NDLS-based chemotherapy in neoadjuvant and metastatic settings. Overall survival (OS) and safety were evaluated for all settings. RESULTS: Of 11 patients (neoadjuvant: 1, adjuvant: 3, and metastatic: 7) in this study, majority had leiomyosarcoma (63.6%, 7/11) followed by extraskeletal myxoid chondrosarcoma (EMC), high grade pleomorphic sarcoma of mandible, malignant fibrous histiocytoma of right thigh, and osteosarcoma of femur (9.1% each, 1/11 each). NDLS plus gemcitabine combination was used in 10 patients (90.9%), and NDLS plus cyclophosphamide was used in one patient with EMC (9.1%). Efficacy evaluation was performed for 7 patients (neoadjuvant: 1/1; metastatic: 6/7). Complete response was reported in one patient (soft tissue sarcoma of mandible) treated in neoadjuvant setting. In metastatic setting, ORR was 50% and DCR was 66.7% (CR: 16.7% (1/6), PR: 33.3% (2/6), SD: 16.7% (1/6)). At a median follow-up of 6.5 months (range: 0.06-20.2 months), median OS was not reached in neoadjuvant and adjuvant settings, but it was 15.8 months in metastatic setting. At least 1 AE was reported in 7 (63.6%) patients. Neutropenia, thrombocytopenia, lymphopenia, and anemia were the hematological AEs, whereas nausea, vomiting, and diarrhea were the most common nonhematological AEs. NDLS treatment was well tolerated without any new safety concerns. CONCLUSION: Nanosomal docetaxel lipid suspension-based chemotherapy was efficacious and well tolerated in the treatment of sarcoma. Further prospective trials are needed to confirm the data.

Patterns of epidermal growth factor receptor testing across 111 tertiary care centers in India: Result of a questionnaire-based survey.

BACKGROUND: We conducted a survey of 111 medical oncologists across India to understand the current pattern of epidermal growth factor receptor (EGFR) mutation testing at their respective centers. METHODS: Medical oncologists from 111 institutes across India were interviewed face to face using a structured questionnaire. They were divided into two groups - Group 1 with in-house EGFR testing and Group 2 who send samples to central/commercial laboratories outside their institutions. Answers of the two groups were analyzed to see the prevailing patterns of EGFR testing and differences between the two groups if any. RESULTS: Ninety-five percent (105/111) of medical oncologists recommended testing for EGFR mutations in patients with adenocarcinoma histology and 40% (44/111) recommended EGFR testing in squamous cell histology. The average time duration to get EGFR test results was 10 days in Group 1 centers versus 18 days in Group 2 centers. Ninety-six percent (106/111) of the medical oncologists from Group 1 centers requested for factoring additional sample for biomarker testing compared to 69% (77/111) of the oncologists from Group 2 centers. Sixty-nine percent (77/111) of medical oncologists in Group 1 centers would prefer to wait for the test results before initiating treatment compared to 46% (51/111) in Group 2. EGFR tyrosine-kinase inhibitors were used in only approximately 60% of patients with diagnosed EGFR mutation in the first line. For patients in whom chemotherapy was initiated while waiting for test results, 50% (56/111) of medical oncologists would prefer to complete 4-6 cycles before switching to targeted therapy. At the time of progression, rebiopsy was possible in approximately 25% of the patients. CONCLUSIONS: Turnaround time for molecular testing should improve so that eligible patients can benefit from targeted therapies in the first line. There is a need to increase the awareness among pulmonologists, oncologists, and interventional radiologists regarding the importance of adequate samples required for molecular tests.

Asymptomatic Emphysematous Pyelonephritis - Positron Emission Tomography Computerized Tomography Aided Diagnostic and Therapeutic Elucidation.

The authors report an interesting coincidental unearthing by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) of a potentially serious medical condition of emphysematous pyelonephritis in a case of nasopharyngeal carcinoma. The management by conservative ureteric stenting and antibiotics was done with gratifying clinical outcome.

CONCORDANCE: A real?world evidence study to evaluate the concordance of detecting epidermal growth factor receptor (EGFR) mutation by circulating tumor DNA* versus tissue biopsy in patients with metastatic non?small cell lung cancer

Background: Molecular tissue testing in non?small cell lung cancer (NSCLC) is done for the assessment of epidermal growth factor receptor (EGFR) mutation. EGFR mutation status is the basis for deciding the targeted treatment option for patients with metastatic NSCLC. The nonavailability of tissue samples and contraindications for biopsy pose a significant challenge. Hence circulating tumor DNA (ctDNA) by liquid biopsy can be a viable alternative for NSCLC patients. Methods: This study was conducted at 15 sites across India. EGFR mutation testing from plasma was done as part of the study at the central laboratory by the next?generation sequencing (NGS) method and EGFR mutation test results from tissue samples (done as part of routine practice) were recorded for all the patients. Results: Out of the total patients enrolled (N = 245) the majority (64.5% n = 158) were men. The median age of patients was 58.0 (range: 26�) years. The concordance between plasma and tissue testing was found to be 82.9% (95% confidence interval [CI]: 77.55 87.45). The sensitivity and specificity of NGS were 68.4% (95% CI: 56.92 78.37) and 90.1% [95% CI: 84.36 94.21) respectively. Plasma testing detected 1.2% (n = 3) and tissue sample testing detected 2.4% (n = 6) positive status of exon 20 T790M EGFR mutation. Out of the total number of patients enrolled 25 were tissue positive and plasma negative while 16 were plasma positive and tissue negative. Conclusions: This real?world study in Indian patients suggests that plasma testing for EGFR mutation analysis is a viable diagnostic option in newly diagnosed advanced/metastatic NSCLC patients. The noninvasive plasma procedure in patients without available/evaluable tumor sample may enable more patients to receive appropriate targeted therapies by providing clinicians with valuable insights into the patient抯 tumor mutation status. ClinicalTrials.gov Identifier: NCT03562819

Robust Reference Intervals for Serum Kappa and Lambda Free Light Chains from a Multi Centre Study Population from Hyderabad, India: Myeloma Diagnostic Implications.

The International Myeloma Working Group considers the serum free light chain (SFLC) assay to be an adjunct to traditional tests. Apart from the FLC ratio, the absolute values of individual free light chains also are gaining importance as they appear to be more relevant in certain clinical settings. Automated assays are available for their determination. As laboratories put new test systems into use catering to different disease populations, they are required by accreditation and certification bodies to verify or establish performance specifications, including reference intervals (RIs) representative of their population. Our aim was to establish local RIs for SFLC in a multicentre representative healthy population using a robust method. There was no significant relationship between SFLC levels and age, gender and creatinine levels. The 95% RI for κSFLC was 4.81 to 33.86mg/L, for ? SFLC was 5.19 to 23.67mg/L and for κ/?SFLC was 0.36 to 2.33, significantly higher than the values given by the manufacturer. The κ/? SFLC ratio at 2.23, covering 100% of the data, showed 72% sensitivity (95% CI=39.0 - 94.0), 100% specificity (95% CI=71.5 - 100.0), 100% PPV (95% CI=21.5 - 100.0), 95% NPV (95% CI=75.4 - 99.9), and 79% accuracy (95% CI=56.0 - 93.0). In the patient group, kit RI for κ /? SFLC ratio classified 45.5% (n=5) as positive vs 9.1% (n=1) positive by the study RI, while the kit RI for kappa FLC classified 90.9% (n=10) as positive vs 54.5% (n=6) , indicating increased probability of false positive test results with the kit RI when applied to our patient population. Appropriate and specific reference intervals and criteria values result in fewer false-positive and false-negative results which means fewer wrong or missed diagnoses.

Non heamoptytic massive Rasmussen's pulmonary artery aneurysm caused by aggressive cavitating squamous cell carcinoma metastasis.

The authors report an extremely rare occurrence of a massive aneurysm of a major pulmonary artery branch vessel caused by adjacent necrotizing aggressive squamous cell carcinoma metastatic mediastinal nodes. Despite the huge size, there was no hemoptysis due to the walling off effect by the necrotic nodes.

Your dilemma, my identity: unusual immunogenetic profiles of pediatric B cell acute lymphoblastic leukemia.

B-cell acute lymphoblastic leukemia (B-ALL) is characterized by CD19 expression, which is one of the most important prerequisites, along with expression of CD10, CD22 and/or CD79a. Rearrangements involving MLL gene are seen in CD10- B-ALL (pro-B cell origin) and t(9;11)(p21;q23) is most commonly reported in acute myeloid leukemia (AML), where it is known to carry very good prognosis in pediatric AMLs and rarely in acute lymphoblastic leukemia (ALL). We report a case of CD10+, CD19- pediatric ALL with rearrangements of MLL gene as a result of t(9;11)(p21;q23), thus conferring a very poor prognosis. The case emphasizes use of comprehensive panel of antibodies for flow cytometric immunophenotyping and cytogenetic correlation for correct diagnosis and prognostication.

Metastatic squamous cell carcinoma thyroid from functionally cured cancer cervix.

The authors report a very unusual occurrence of a metastatic squamous carcinoma to thyroid gland from a treated squamous cell carcinoma cervix 12 years before with no recurrence at the primary site. The case also has an additional complexity of rapid progression of the metastatic thyroid carcinoma to wide spread dissemination to lungs and bones while on concurrent chemo radio therapy confirming the aggressiveness of the entity.

Your dilemma, my identity: Unusual immunogenetic profiles of pediatric B cell acute lymphoblastic leukemia.

B-cell acute lymphoblastic leukemia (B-ALL) is characterized by CD19 expression, which is one of the most important prerequisites, along with expression of CD10, CD22 and/or CD79a. Rearrangements involving MLL gene are seen in CD10− B-ALL (pro-B cell origin) and t(9;11)(p21;q23) is most commonly reported in acute myeloid leukemia (AML), where it is known to carry very good prognosis in pediatric AMLs and rarely in acute lymphoblastic leukemia (ALL). We report a case of CD10+, CD19− pediatric ALL with rearrangements of MLL gene as a result of t(9;11)(p21;q23), thus conferring a very poor prognosis. The case emphasizes use of comprehensive panel of antibodies for fl ow cytometric immunophenotyping and cytogenetic correlation for correct diagnosis and prognostication. KEY WORDS: Acute lymphoblastic leukemia, CD19, MLL gene, t(9;11)(p21;q23)